Measurement of circulating insulin concentrations in serum or plasma may improve the classification and management ofdiabetes mellitus, assist in treating people with insulin resistance and provide an additional indicator for coronary artery disease (CAD). Four large prospective studies (Diabetes Care 1979;2:131;Diabetes Care 1979;2:154;Diabetologia 1980;19:205;Diabetologia 1991;34:356) have shown that hyperinsulinemia is a predictor of CAD. The greatest association of hyperinsulinemia with CAD has been found in Finland in a population with a very high frequency of CAD (Diabetes Care 1979;2:131). Results of a prospective investigation of 2103 men from Quebec, Canada (N Eng J Med 1996;334:95) clearly showed that high fasting insulin concentrations are an independent predictor of CAD. Several other studies (Stroke 1995;26:956;Circulation 1995;91:1432;Stroke 1996;27:37;Hypertension 1996;28:593) have shown a relationship between carotid wall atherosclerotic lesions, angina, and insulin resistance. Thus it is critical that research considered in the formulation of clinical guidelines be based on harmonized insulin results. Such harmonization will allow aggregation of information from multiple investigations, enabling evidence-based criteria to incorporate insulin concentrations consistently across assays and laboratories. A Work Group of the American Diabetes Association in conjunction with the National Institute of Diabetes and Digestive and Kidney Diseases, the European Association for the Study of Diabetes, the Centers for Disease Control and Prevention, and the International Federation of Clinical Chemistry was established to develop guidelines for measurement performance requirements and to develop a standardization program to achieve sufficient agreement between methods. Recent evaluations (Clin Chem 2007;53:711;Clin Chem 2007;53:1462;Clin Chem 2007;53:922;Clin Chem 2009;55:1011) of routine methods for measuring circulating insulin concentrations concluded that although concordance of methods has seen improvement, harmonization among methods needs further improveement.